Project summary: The mouse skin represents an exceptional model to study individual proteins in different cell types and their respective contribution to a stratified epidermal tissue. We have found a novel protein, sSHIP, which may be critical for normal epidermal homeostasis and tissue repair. sSHIP is produced from an internal promoter, of the SHIP1 gene. To determine the tissue specific expression pattern of the sSHIP promoter we produced transgenic mouse lines expressing enhanced green fluorescence protein (GFP) from the sSHIP promoter. Analysis of the embryonic skin indicated strong GFP expression from E11.5-E18.5 throughout the basal layer. In the adult, the basal layer of the epidermis has lost expression of GFP. However, GFP+ cells become apparent in the bulge region of the hair follicle at the earliest stages of the hair follicle growth phase (anagen). In addition, GFP expression continues in the outer root sheath of the hair follicle throughout its growth indicating a critical role for sSHIP in both the initiation and maintenance of anagen. Furthermore, we found epidermal depilation of the 11.5kb-GFP transgenic mice lead to the reactivation of the 11.5-kb sSHIP promoter in the bulge region of the hair follicle as well as the interfollicular epidermis. Endogenous sSHIP mRNA expression was induced with kinetice similar to the GFP transgene induction. These findings may indicate a dual role for sSHIP in restratification of the interfollicular epidermis and initiation of anagen from stem cells. The long-term objectives of this application are to determine the role of sSHIP in epidermal development, epidermal homeostasis, epidermal injury and skin carcinogenesis. To carry out this objective we will use both conditional transgenic and knockout mice. Furthermore we will study the regulation of the sSHIP promoter by the p63 transcription factor. Work from this proposal will aid in the better understanding of the development of the skin. Relevance: The research in this proposal is aimed at understanding the expression and function of a single protein which may be critical for the development of the epidermis. [unreadable] [unreadable] [unreadable]